Liver physiology 2: The liver as a storage organ

Question 1

what are the functions of the liver?

Answer 1

• Carbohydrate metabolism
• Fat metabolism
• Protein metabolism
• Hormone metabolism
• Toxin/Drug metabolism and excretion
• Storage
• Bilirubin metabolism and excretion

Question 2

iron metabolism

Answer 2

Iron taken in as dietary iron e.g. in spinach, absorbed by the duodenum where it is converted into plasma transferrin (transports ferritin in the blood) which can be used in the muscle cells or bone barrow or stored in the liver and sometimes macrophages until it is ready to be used in the body

Question 3

what is Ferritin

Answer 3

• Large spherical protein consisting of 24 noncovalently linked sub units
• Subunits form a shell surrounding a central core.
• Core contains up to 5000 atoms of iron.
• Ferritin found in the cytoplasm of cells but can also be found in the serum.
• Concentration of ferritin is directly proportional to the total iron stores in the body.
• Often used as the way test for iron deficiency as more reliable and less likely to change

Question 4

Ferritin excess

Answer 4

Excess iron storage disorders:
•	Hereditary haemochromatosis
•	Haemolytic anaemia
•	Sideroblastic anaemia
•	Multiple blood transfusions
•	Iron replacement therapy
Non-Iron overload:
•	Liver disease
•	Some malignancies
•	Significant tissue destruction
•	Acute phase response:
o	Inflammation
o	Infection
o	Autoimmune disorders

Question 5

Ferritin deficiency

Answer 5

The only known cause of a low ferritin is iron deficiency.
This can result in anaemia.
o Ferritin less than 20 µg/L indicates depletion
o Ferritin less than 12 µg/L suggests a complete absence of stored iron.

Question 6

RDA

Answer 6

recommended daily allowance

Question 7

AI

Answer 7

adequate intake where no evidence to determine RDA

Question 8

vitamins act as

Answer 8

• Gene activators
• Free-radical scavengers
• Coenzymes or cofactors in metabolic reactions
• Excessive vitamin ingestion can result in toxicity.

Question 9

what type of vitamins require more regular intake?

Answer 9

water soluble vitamins e.g B & C as they pass more readily through the body

Question 10

vitamin A (retinoids)

Answer 10

Fat soluble
Vertebrates ingest retinal directly from meat or produce retinal from carotenes
functions:
Vision:
o Used to form rhodopsin in the rod cells in the retina.
Reproduction:
o Spermatogenesis in male
o Prevention of foetal resorption of female
Growth
Stabilisation of cellular membranes
requirements: 0.6 mg/day in men, 0.7 mg/day in women

Question 11

vitamin A deficiency

Answer 11

• Rare in affluent countries as vitamin A levels drop only when liver stores are severely depleted.
• Deficiency may occur due to fat malabsorption
Clinical Features:
o Night blindness
o Xeropthalmia
o Blindness

Question 12

vitamin A excess

Answer 12

Acute:
•	Abdominal pain, nausea and vomiting
•	Severe headaches, dizziness, sluggishness and irritability
•	Desquamation of the skin
Chronic:
•	Joint and bone pain
•	Hair loss, dryness of the lips
•	Anorexia
•	Weight loss and hepatomegaly
Carotenemia:
•	Reversible yellowing of the skin
•	Does not cause toxicity

Question 13

vitamin D functions

Answer 13

fat soluble
Functions:
o	Increased intestinal absorption of calcium
o	Resorption and formation of bone
o	Reduced renal excretion of calcium

Question 14

vitamin D deficiency

Answer 14

Deficiency:
o Demineralisation of bone:
o Rickets in children
o Osteomalacia in adults

Question 15

vitamin E

Answer 15

fat soluble 
Stored in:
•	Non-adipose cells such as liver and plasma – labile and fixed pool
•	Adipose cells – fixed pool 
Important antioxidant
Vitamin E requirements:
•	4 mg/day in men
•	3 mg/day in women

Question 16

vitamin E deficiency

Answer 16

Caused by:
o	Fat malabsorption (e.g. cystic fibrosis)
o	Premature infants
o	Rare congenital defects in fat metabolism e.g. abetalipoproteinaemia.
Clinical manifestations:
o	Haemolytic anaemia
o	Myopathy
o	Retinopathy
o	Ataxia
o	Neuropathy

Question 17

vitamin E excess

Answer 17

Vitamin E excess is relatively safe in excess

Question 18

Vitamin K sources and functions

Answer 18

fat soluble
Vitamin K is rapidly taken up by the liver but then is transferred to very low-density lipoproteins and low density lipoproteins which carry it into the plasma.
Sources:
• Vitamin K1 (phylloquinone) - Synthesized by plants and present in food
• Vitamin K2 (menaquinone) - Synthesized in humans by intestinal bacteria
• Synthetic vitamin K’s: K3 (menadione), K4 (menadiol)
Functions:
Vitamin K is responsible for the activation of some blood clotting factors.
Necessary for liver synthesis of plasma clotting factors II, VII, IX and X.
Can be assessed by measuring prothrombin time.

Question 19

vitamin K deficiency

Answer 19

• Haemorrhagic disease of the newborn: Vitamin K injection given to newborn babies
• Rare in adults, unless on warfarin.

Question 20

vitamin K excess

Answer 20

• K1 is relatively safe
• Synthetic forms are more toxic
• Can result in oxidative damage, red cell fragility and formation of methaemoglobin.

Question 21

Vitamin C

Answer 21

water soluble 
Found in:
•	Fresh fruit and vegetables
Adults need 40 mg/day
Functions:
•	Collagen synthesis
•	Antioxidant
•	Iron absorption

Question 22

vitamin C deficiency

Answer 22

Scurvy
•	Easy bruising and bleeding
•	Teeth and gum disease
•	Hair loss
•	Treatment with vitamin C improves symptoms quickly (Joint pain gone within 48 hours, Full recovery within two weeks)

Question 23

vitamin C excess

Answer 23

• Doses > 1g/day can cause GI side effects

* No evidence that increased vitamin C reduces the incidence or duration of colds.

Question 24

Vitamin B12 (Cobalamins)

Answer 24

water soluble
Two active forms: Methylcobalamin, 5-deoxyadenosylcobalamin
• Released from food by acid and enzymes in the stomach
• Binds to R protein to protect it from stomach acid
• Released from R proteins by pancreatic polypeptide.
• Intrinsic factor (IF) produced by the stomach needed for absorption.
• IF-B12 complex absorbed in the terminal ileum.
• B12 is stored in the liver.

Question 25

vitamin B12 deficiency

Answer 25

Causes:
• Pernicious anaemia – autoimmune destruction of IF-producing cells in stomach.
• Malabsorption – lack of stomach acid, pancreatic disease, small bowel disease.
• Veganism
Symptoms: Macrocytic anaemia, Peripheral neuropathy in prolonged deficiency

Question 26

Folate

Answer 26

water soluble
• Folate is found in may foods fortified with folic acid.
• Individuals have higher requirements in pregnancy.
• Functions as a coenzyme in methylation reactions, DNA synthesis, synthesis of methionine from homocysteine.

Question 27

folate deficiency

Answer 27

Causes:
• Malabsorption
• Drugs that interfere with folic acid metabolism (anticonvulsants, methotrexate)
• Disease states that increase cell turnover (e.g. leukaemia, haemolytic anaemia, psoriasis)
Symptoms:
• High homocysteine levels
• Macrocytic anaemia
• Foetal development abnormalities (neural tube defects)

Question 28

clotting factors

Answer 28

• Intrinsic pathway activated by contact.
• Extrinsic pathway activated by FVII coming in contact with tissue factor.
• Initiates a cascade which ultimately results in fibrin clot formation.
Produced in the liver
o I (Fibrinogen)
o II (Prothrombin)
o IV
o V
o VI
o VII
The performance of the clotting pathways can be measured using:
• Prothrombin time (PT) (extrinsic pathway)
• International normalised ratio (INR)
• Activated partial thromboplastin time (aPTT) (intrinsic pathway)
A prolonged PT may indicate a deficiency in the synthetic capacity of the liver.
Prolonged PT is not specific for liver disease:
• DIC
• Severe GI bleeding
• Some drugs
• Vitamin K deficiency